1. Field of the invention
The present disclosure relates generally to medical methods and delivery systems. More particularly, the present disclosure relates to methods and systems for delivering therapeutic agents such as toxins or non-toxins to mucosa targets in a nasopharyngeal space.
Rhinitis is commonly referred to as “stuffy nose,” and results from inflammation and swelling of the mucus membranes lining the nasal cavity. Rhinitis falls into two major categories—allergic and non-allergic (or vasomotor). Chronic rhinitis can result in chronic inflammation of the nasal passages resulting in sinusitis, an infection or inflammation of the paranasal sinuses. Rhinitis includes the symptoms of rhinorrhea which is commonly referred to as “runny nose.” Rhinorrhea describes the effluence of mucus from the lining of the nasal passages, nasopharynx, or paranasal sinuses. Rhinorrhea can be a symptom of a number of diseases such as the common cold, or sinusitis.
Allergic rhinitis is an immunologic response modulated by immunoglobulin E (IgE) and characterized predominantly by sneezing, rhinorrhea, nasal congestion, and pruritus of the nose. It may be seasonal (a condition commonly referred to as hay fever) or perennial. The seasonal form is caused by allergens released during tree, grass, or weed pollination, whereas the perennial form is caused by allergies to animal dander, dust mites, or mold spores with or without associated pollinosis. Data also suggest that urban air pollutants from automobiles and other sources may have an adjunctive effect.
Non-allergic rhinitis may be caused by anatomic pathologies such as blockages, as seen in the case of sinusitis. Symptoms may include sneezing, itching, nasal congestion, and a runny nose. Non-allergic rhinitis is a diagnosis of rhinitis without any IgE mediation, as documented by allergen skin testing. Hence, the rhinorrhea, sneezing, pruritus, and congestion do not result from allergy or hypersensitivity and continue to persist, whether continuously or sporadically. Non-allergic rhinitis affects 5-10% of the population. Non-allergic rhinitis has 7 basic subclassifications, including infectious rhinitis, non-allergic rhinitis with eosinophilia syndrome (NARES), occupational rhinitis, hormonal rhinitis, drug-induced rhinitis, gustatory rhinitis, and vasomotor rhinitis. Patients may or may not present with the same symptoms seen in allergic rhinitis.
While numerous treatments for rhinitis have been proposed over the years, no single treatment is optimum for all patients or all conditions. Most commonly, hay fever and other forms of rhinitis are treated with antihistamines which block the inflammatory response. While effective, many antihistamines are also undesirable because they can cause drowsiness, or they may have a limited duration of effect, and they can present the patient with an on-going cost associated with continuous purchase of the drugs.
Recently, a longer term therapy for rhinitis which relies on the use of botulinum toxin (BoNT) for blocking mucus production by mucus-producing cells in the nasal membrane has been proposed. Botulinum toxin and other neurotoxins are capable of disabling adrenergic cells, including epithelial or goblet cells which are responsible for the majority of mucus production in the nasal cavity membrane. It has been published in the scientific literature that introduction of botulinum toxin into the nasal passages of canines can reduce mucus secretion by a significant amount.
While the use of botulinum toxin appears to hold promise for long term rhinitis treatment, it faces a number of challenges before it is suitable for wide spread use in humans. In particular, botulinum toxin is a neurotoxin which could have significant negative effects on a patient if accidentally released outside of the targeted nasal passages. Inadvertent distribution of the toxin to muscles of the oropharynx, mouth, tongue, or elsewhere could result in serious complications to the patient. Injection of the toxin helps to overcome some of these issues by directing the toxin to the target area and injection can performed relatively quickly. However, injections also have some challenges that could be overcome, including the fact that injection of the neurotoxin typically requires a local anesthetic to be used, and the fact that many patients are uncomfortable when seeing a needle being inserted into their nostril. Moreover, the use of a needle to inject a toxin deep within the nasal cavity can be very difficult. Topical application of toxins also may have short comings, particularly in terms of the accuracy of delivery of the toxin. For example, the use of botulinum-soaked gauze pads for delivering the toxin to the nasal cavities, as reported in the scientific literature, have limited ability to uniformly and selectively deliver the botulinum to the regions having high concentrations of preferred target cells, such as epithelial or goblet cells in the nasopharynx. Sponges inserted into the nose can be difficult to place, and are hard and uncomfortable when dry, and lack rigidity when wet. Inadvertent compression of a soaked sponge (e.g. against an obstacle during delivery) can result in the drug being squeezed out of the sponge too quickly for adjacent mucosa to absorb the drug, and often in the wrong location. Loading the sponge with a therapeutic agent can also be difficult and time consuming. Aerosol systems have also been proposed for use in delivering a therapeutic agent, but again, precise control of toxin delivery can be a challenge, especially given the dispersement under pressure. Drug eluting balloons have also been suggested for delivery of a therapeutic agent to the sinuses, but require precise positioning.
For these reasons, it would be desirable to provide improved methods and systems for delivering the correct dose of therapeutic agent in a controlled manner to a target treatment site. Such improved methods and systems are preferably used to deliver a toxin, such as botulinum toxin to the nasal membrane of a patient, particularly in a patient suffering from rhinitis or other conditions associated with nasal inflammation and conditions, such as sinus headaches and migraine headaches. Other therapeutic agents including non-toxins may also be delivered. Such systems and methods preferably allow easy delivery without requiring visualization devices such as endoscopes, and preferably do not require anesthesia. The devices preferably have a compact initial shape for insertion and may be easily deployed or activated to expand and fill the desired area of the nasal cavity. The methods and systems should be capable of providing for selective and repeatable delivery of an appropriate dose of the toxins to a defined target areas within the nasal cavities, including particular paranasal sinuses, the nasopharynx, and in some cases substantially the entire nasal cavity. The systems and methods should provide for the safe, accurate and effective delivery of a proper dose of the toxins, and in particular should reduce or eliminate the risk of toxin being delivered to non-targeted tissues outside of the nasal cavity. At least some of these objectives will be met by the inventions described herein below.
2. Description of the Background Art
Patents and publications related to delivery of a toxin to the nasal cavity include U.S. Pat. Nos. 5,766,605 and 6,974,578; and U.S. Patent Publication No. 2005/0281751. Related scientific literature includes Sharri et al. (1995) Otolaryngol. Head Neck Surg. 112: 566-571 which further discusses the work disclosed in U.S. Pat. No. 5,766,605. Ünal et al. (2002) Acta Otolaryngol 123: 1060-1063 describes the injection of botulinum toxin A into the turbinates of patients suffering from allergic rhinitis. The use of catheters and other devices for the energy-mediated delivery of botulinum light chain is described in commonly owned co-pending U.S. patent application Ser. No. 11/750,967, the entire contents of which are incorporated herein by reference.